diseases of renal interstitium

8/9/2019 Diseases of Renal Interstitium

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DISEASES OF RENAL

TUBULES ANDINTERSTITIUM


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(1) inflammatory involvement of the

tubules and interstitium (interstitial

nephritis)

(2) ischemic or toxic tubular injury, leading

to acute tubular necrosis and acute renal

failure.


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Tubulointerstitial Nephritis

Acute Pyelonephritis

Suppurative inflammation of the kidney and the

renal pelvis, is caused by bacterial infection

Cause

Proteus, Klebsiella, Enterobacter, and Pseudomonas,

Staphylococci and Streptococcus faecalis may also

cause pyelonephritis, but they are uncommon

urinary tract manipulations or have congenital oracquired anomalies of the lower urinary tract


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Etiology

Urinary obstruction, congenital or acquired Instrumentation of the urinary tract, most commonly

catheterization

Vesicoureteral reflux.

Pregnancy.

Patient's sex and age. After the first year of life (when congenitalanomalies in males commonly become evident) and as far asaround age 40 years, infections are much more frequent infemales. With increasing age, the incidence in males rises as aresult of the development of prostatic hyperplasia and frequentinstrumentation.

Preexisting renal lesions, causing intrarenal scarring andobstruction

Diabetes mellitus, in which acute pyelonephritis is caused byincreased susceptibility to infection and neurogenic bladderdysfunction

Immunosuppression and immunodeficiency.


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Pathology 2 routes

Through the bloodstream (hematogenous) septicemia

infective endocarditis

From the lower urinary tract (ascending infection adhesion to the urothelial lining by bacterial fimbriae

colonization of the distal urethra access to the bladder(urethral instrumentation, including

catheterization and cystoscopy )


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Obstruction at the level of the urinary bladder

incomplete emptying and increased residual volumeof urine.

bacteria introduced into the bladder can multiplyundisturbed

incompetence of the vesicoureteral orifice congenital defect

acquired in individuals with a flaccid bladder resulting from

spinal cord injury and with neurogenic bladder dysfunctionsecondary to diabetes

bacteria ascend the ureter into the pelvis


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Morphology normal in size or enlarged

discrete, yellowish,

raised abscesses aregrossly apparent on therenal surface

They may be widelyscattered or limited to oneregion of the kidney, or

they may coalesce to forma single large area ofsuppuration.


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Histologic feature of acute pyelonephritis issuppurative necrosis or abscess formation withinthe renal parenchyma. In the early stages the

suppuration is limited to the interstitial tissue, but laterabscesses rupture into tubules. Large masses ofintratubular neutrophils ,white cell casts found inthe urine.

The glomeruli are not affected

When obstruction is prominent, the pus may beunable to drain and thus fills the renal pelvis, calyces,and ureter, producing pyonephrosis.


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A second form of pyelonephritis -papillary necrosis.

diabetics who develop acute pyelonephritis complicate acute pyelonephritis when there is significant

urinary tract obstruction.

chronic interstitial nephritis associated with analgesic abuse

ischemic and suppurative necrosis of the tips of the renalpyramids (renal papillae).

The pathognomonic gross feature- sharply defined gray-white to yellow necrosis of the apical two-thirds of thepyramids. One papilla or several or all papillae may beaffected.

Microscopically The papillary tips show characteristic coagulative necrosis,

with surrounding neutrophilic infiltrate

When the bladder is involved acute orchroniccystitis results.

In long-standing cases, the bladder may be grosslyhypertrophic, with trabeculation of its walls, or it maybe thinned and markedly distended from retention ofurine


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Course

Sudden onset pain at the costovertebral angle

chills, fever, and malaise.

pyuria and bacteriuria.

dysuria, frequency, urgency

benign and self-limited. no longer than a week

bacteriuria may persist much longer

usually unilateral and thus the patient dosent developrenal failure

The development of papillary necrosis is associatedwith a much poorer prognosis. Sepsis and, often,renal failure.

Diagnosis Leukocytes ("pus cells") by urinalysis and urine

culture.


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Chronic Pyelonephritis and Reflux

Nephropathy Interstitial inflammation and scarring of the renal

parenchyma is associated with grossly visiblescarring and deformity of the pelvicalycealsystem

Two forms: chronic obstructive pyelonephritis

Recurrent infections superimposed on diffuse or localizedobstructive lesions lead to recurrent bouts of renal

inflammation and scarring, which eventually cause chronicpyelonephritis. Bilateral, congenital anomalies of the urethra (posterior urethral

valves)

unilateral, calculi and unilateral obstructive lesions of the ureter.


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Chronic reflux-associated pyelonephritis.

more common form of chronic pyelonephritic scarring

superimposition of a UTI on congenital vesicoureteral refluxand intrarenal reflux.

Reflux may be unilateral or bilateral; thus, the resultant renal

damage either may cause scarring and atrophy of one kidney

or may involve both and lead to chronic renal insufficiency


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Morphology One or both kidneys

diffusely or in patches.

Even when involvement is bilateral, the kidneys are not equallydamaged and therefore are not equally contracted. This unevenscarring is useful in differentiating chronic pyelonephritis fromvascular sclerosis and chronic GN

The hallmark of chronic pyelonephritis is scarring involving thepelvis or calyces, or both, leading to papillary blunting andmarked calyceal deformities

The microscopic changes are largely nonspecific Uneven interstitial fibrosis and an inflammatory infiltrate of

lymphocytes, plasma cells


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Dilation or contraction of tubules, with atrophy of the liningepithelium. Many of the dilated tubules contain pink to blue,glassy-appearing PAS-positive casts known as colloid casts thatsuggest the appearance of thyroid tissue, hence the descriptive

term thyroidization. Often, neutrophils are seen within tubules.

Chronic inflammatory infiltration and fibrosis involving thecalyceal mucosa and wall.Vascular changes similar to those ofbenign arteriolosclerosis caused by the frequently associatedhypertension

.Although glomeruli may be normal, in most cases,glomerulosclerosis is seen in areas of better preserved renalparenchyma. Such changes represent secondary sclerosiscaused by maladaptive changes secondary to nephron loss.


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Course

come to medical attention relatively late

hypertension

Pyelograms show the affected kidney to be

asymmetrically contracted blunting and deformity of

the calyceal system

If the disease is bilateral and progressive, tubulardysfunction occurs with loss of concentrating ability,

manifested by polyuria and nocturia


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Drug-Induced Interstitial Nephritis

Acute Drug-Induced Interstitial Nephritis This is an adverse reaction to any of an increasing number of drugs

Occurs with synthetic penicillins (methicillin, ampicillin ), other

synthetic antibiotics (rifampin ), diuretics (thiazides), nonsteroidalanti-inflammatory agents, and numerous other drugs (phenindione,cimetidine).

Pathogenesis immune mechanism as

latent period

eosinophilia and rash onset of nephropathy is not dose related

recurrence of hypersensitivity after re-exposure


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Serum IgE levels are increased

Mononuclear or granulomatous infiltrate, together withpositive skin tests to drugs

Pathogenesis drugs act as haptens

during secretion by tubules, covalently bind to somecytoplasmic or extracellular component of tubularcells and become immunogenic.

The resultant tubulointerstitial injury is then caused byIgE- and cell-mediated immune reactions to tubularcells or their basement membranes


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Morphology Interstitium, shows pronounced edema and infiltration by

mononuclear cells, principally lymphocytes and macrophages

Eosinophils and neutrophils may be present, often in largenumbers

Methicillin, thiazides, rifampin, interstitial non-necrotizinggranulomas with giant cells may be seen.

The glomeruli are normal except in some cases caused bynonsteroidal anti-inflammatory agents when the hypersensitivity

reaction also leads to podocyte foot process effacement (MCD-like lesion), and the nephrotic syndrome develops concurrently


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Course

Disease begins about 15 days after exposure to the

drug Fever, eosinophilia, a rash, renal abnormalities.

hematuria, minimal or no proteinuria, and leukocyturia

(sometimes including eosinophils).

A rising serum creatinine or acute renal failure witholiguria in about 50% of cases, particularly in older

patients


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Analgesic Nephropathy consume large quantities of analgesics or mixtures containing some

combination

associated with renal papillary necrosis Papillary necrosis is the initial event, and the interstitial nephritis in

the overlying renal parenchyma is a secondary phenomenon

Acetaminophen , a phenacetin metabolite, injures cells by bothcovalent bindingand oxidative damage.

The ability of aspirin to inhibit prostaglandin synthesis suggests thatthis drug may induce its potentiating effect by inhibiting thevasodilatory effects of prostaglandin and predisposing the papilla toischemia

Thus, the papillary damage may be caused by a combination of two


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Morphology

necrotic papillae appear yellowish brown, as a

result of the accumulation of breakdown products of

phenacetin and other lipofuscin-like pigments

Later on, the papillae may shrivel, be sloughed off,

and drop into the pelvis. Microscopically, the papillae show coagulative

necrosis

dystrophic calcification may occur

cortex drained by the necrotic papillae shows tubularatrophy, interstitial scarring, and inflammation.

The small vessels in the papillae and urinary tract

submucosa exhibit characteristic PAS-positive

basement membrane thickening


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Clinical Course

chronic renal failure, hypertension, and anemia.

The anemia results in part from damage to red cellsby phenacetin metabolites.

Cessation of analgesic intake may stabilize or even

improve renal function.

Complication -increased incidence oftransitional-cell carcinoma of the renal pelvis or bladder


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Acute Tubular Necrosis Reversible renal lesion that arises in a variety of

clinical settings characterized morphologically bydamaged tubular epithelial cells and clinically byacute suppression of renal function

It is the most common cause of acute renalfailure.

Causes

Nephrotoxic ATN heavy metals (e.g., mercury); organic solvents (e.g., carbon

tetrachloride); and a multitude of drugs such as gentamicinand other antibiotics, and radiographic contrast agents

.


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period of inadequate blood flow to the peripheral

organs like (inischemic ATN) severe trauma

acute pancreatitis

Septicemia

hypotension and shock. The pattern of ATN associated with

shock is called Mismatched blood transfusions hemolytic crises

Myoglobinuria


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Other causes of acute renal failure (urine flowfalls within 24 hours to less than 400 mL perday) include (1) severe glomerular diseases manifesting as RPGN,

(2) diffuse renal vascular diseases such asmicroscopic polyangiitis and thromboticmicroangiopathies,

(3) acute papillary necrosis associated with acute

pyelonephritis, (4) acute drug-induced interstitial nephritis, and

(5) diffuse cortical necrosis.


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Pathogenesis

1) tubular injury and

2) persistent and severe disturbances in blood flowresulting in diminished oxygen and substrate delivery

to tubular cells

factors predispose the tubules to toxic injury,

vast electrically charged surface for fluid reabsorption

active transport systems for ions and organic acids

the capability for effective concentration


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Pathogenesis of ATN due to structral

alterations


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Pathogenesis due to hemodynamic changes

Effect of intra renal vasoconstriction reduced glomerular plasma flow

reduced oxygen delivery to the functionally importanttubules in the outer medulla (thick ascending limb andstraight segment of the proximal tubule)

Intrarenal vasoconstriction caused by Renin-angiotensin, thromboxane A2

sympathetic nerve activity), some triggered by theincreased distal sodium delivery

the current opinion is that vasoconstriction ismediated by sublethal endothelial injury, leading toincreased release of the endothelial vasoconstrictorendothelin and decreased production of vasodilatorynitric oxide and prostaglandins


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Morphology

Necrosis of short segments of the tubules. Most of

the lesions in the straight portions of the proximal

tubule and the ascending thick limbs

widespread overt necrosis of tubular cells is

uncommonly seen in renal biopsy

often a variety oftubular injuries,

attenuation of proximal tubular brush borders,

blebbing and sloughing of brush borders vacuolization of cells, and detachment of tubular cells from

their underlying basement membranes with sloughing of cells

into the urine.


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proteinaceous casts in the distal tubules and

collecting ducts. (consist of Tamm-Horsfall protein

(secreted normally by tubular epithelium) along with

hemoglobin and other plasma proteins). When crush

injuries have produced ATN, the casts are composed

of myoglobin.

interstitium usually shows generalized edema along

with a mild inflammatory infiltrate consisting ofpolymorphonuclear leukocytes, lymphocytes, and

plasma cells


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In toxic ATN necrosis is most prominent in theproximal tubule, and the tubular basementmembranes are generally spared.

If the patient survives for a week, epithelialregeneration becomes apparent in the form of a lowcuboidal epithelial covering and mitotic activity in thepersisting tubular epithelial cells.

Except where the basement membrane is destroyed,

regeneration is total and complete.


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Course

Initiation phase

lasting about 36 hours

dominated by the inciting medical, surgical, or obstetric event

causing ATN.

renal involvement is a slight decline in urine output with a rise

in serum creatinine.

oliguria explained on the basis of a transient decrease in

blood flow to the kidneys.

Maintenance phase

second to the sixth day

Urine output falls markedly, usually to between 50 and 400

mL per day (oliguria)


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complete anuria is rare.

Oliguria may last a few days or persist as long as 3 weeks.

uremia and fluid overload

With good care, survival is the rule

Recovery phase

Steady increase in urine volume, reaching as much as about

3 L/day over the course of a few days.

As tubular function is still deranged, serious electrolyte

imbalances may occur

increased vulnerability to infection.

25% of deaths from ATN occur during this phase.

diseases of renal interstitium

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